CROI 2017 Abstract e-Book

Abstract eBook

Oral Abstracts

83 A RANDOMISED CONTROLLED TRIAL OF INDUCTION THERAPY OF TALAROMYCES MARNEFFEI INFECTION Thuy Le 1 , Nguyen V. Kinh 2 , Nguyen Le Nhu Tung 3 , Thanh Thuy Pham Thi 4 , Pham T. Phuc 5 , Doan T. Hanh 6 , Jeremy Day 1 , Guy Thwaites 1 , Marcel Wolbers 1 , for the IVAP Investigators 1 Oxford Univ Clinical Rsr Unit in Vietnam, Ho Chi Minh, Vietnam, 2 Natl Hosp for Trop Diseases, Hanoi, Vietnam, 3 Hosp for Trop Diseases, Ho Chi Minh City, Vietnam, 4 Bach Mai Hosp, Hanoi, Vietnam, 5 Viet Tiep Hosp, Hai Phong, Vietnam, 6 Uong Bi Hosp, Quang Ninh, Vietnam Background: Talaromyces (formerly Penicillium) marneffei infection is a leading cause of HIV-related death in South and Southeast Asia. Amphotericin B deoxycholate (dAmB) is recommended for induction therapy but has significant side effects and limited availability. Itraconazole is well-tolerated, is more widely-used, and in large case series is shown to be similar to dAmB in mortality and clinical outcomes. However, these drugs have never been tested in clinical trials. Methods: In this open-label non-inferiority trial, we randomly assigned 440 HIV-infected adults with microbiology-confirmed talaromycosis in five major referral hospitals in Vietnam to receive dAmB (219 patients) or itraconazole (221 patients) for two weeks, followed by itraconazole consolidation and maintenance therapy in all patients. The primary outcome was mortality at two weeks. The secondary outcomes were survival until week 24, time to clinical resolution, early fungicidal activities, disease relapse, immune reconstitution inflammatory syndrome (IRIS), and grade III or higher adverse events. Results: The mortality at two weeks was 6.5% in the dAmB group and 7.4% in the itraconazole group (absolute risk difference, 0.9%; 95% confidence interval [CI], -3.9% - 5.7%; non-inferiority P<0.0001); however, mortality at 24 weeks was 11.3% and 21.0%, respectively (hazard ratio, 1.88; 95% CI, 1.15 - 3.09; P=0.012). Consistent with the higher mortality in the itraconazole group, clinical resolution and fungal clearance were slower (P=0.049 and P<0.0001), and relapse and IRIS were more common (P=0.005 and P=0.0001). Patients on dAmB experienced more infusion reactions (P<0.0001), renal failure (P=0.006), hypokalemia (P=0.0009), hypomagnesemia (P=0.021), and anaemia (P=0.012), but these were not considered life-threatening. Conclusion: dAmB is found to be superior to itraconazole in the induction therapy of talaromycosis in measures of overall mortality, clinical response, disease complications, and fungicidal activity, and should be made available for patients in Asia.

Oral Abstracts

84 RESISTANCE EMERGENCE IN MACAQUES ADMINISTERED CABOTEGRAVIR LA DURING ACUTE INFECTION Jessica Radzio 1 , Olivia Council 1 , Mian-er Cong 1 , James Mitchell 1 , Shanon Ellis 1 , Wei Huang 2 , William Spreen 3 , Walid Heneine 1 , Gerardo Garcia-Lerma 1 1 CDC, Atlanta, GA, USA, 2 Monogram BioScis, San Francisco, CA, USA, 3 ViiV Hlthcare, Rsr Triangle Park, NC, USA

Background: Drug resistance in individuals who acquire HIV while taking pre-exposure prophylaxis (PrEP) has been rare and mostly limited to those who initiate PrEP during unrecognized acute infection. A long-acting injectable formulation of the HIV integrase inhibitor (INI) cabotegravir (CAB LA) is currently in clinical development as a PrEP agent. We used a macaque model of simian HIV (SHIV) infection to model risks of drug resistance emergence associated to CAB LA initiation during undiagnosed HIV infection. Methods: Six rhesus macaques were infected intravenously with a pathogenic RT-SHIV containing the SIVmac239 integrase, and received 50 mg/kg of CAB LA intramuscularly prior to seroconversion. Macaques received 2 subsequent CAB LA injections 4 weeks apart to sustain plasma drug levels above 4 times the protein-adjusted IC90 (4xPA-IC90) and model humans treated with 600-800 mg every 8-12 weeks. SHIV viremia and mucosal virus shedding was monitored by RT-PCR. Integrase mutations in plasma and rectal/vaginal fluids were monitored by population sequencing. Drug concentrations were measured by LC-MS.

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CROI 2017